Investigations
1st investigations to order
serology
Test
Serological testing is recommended in patients with suspected disease. Test serum and/or cerebrospinal fluid (CSF) for the presence of WNV-specific immunoglobulin M (IgM) antibodies using a commercially available immunoassay. Serum and CSF samples are recommended if neurological symptoms are present.[36][37] Results are usually available in 24-48 hours.
Presence of WNV-specific IgM antibodies in serum and/or CSF provides good evidence of recent infection. The detection of IgM antibodies in the CSF indicates CNS infection. IgM antibodies are detectable for 3-8 days after symptom onset, and may persist for up to 3 months, or in some cases, up to 12 months or longer.[36][37] Sensitivity is nearly 100% after the eighth day of illness.[39][54][55]
A positive result may indicate past infection with WNV or antibody cross-reactivity to other flaviviruses (e.g., yellow fever virus, Japanese encephalitis virus, dengue virus) from exposure via infection or vaccination. A negative result does not rule out the diagnosis. A false-negative result is possible if the sample was collected in the first few weeks after symptom onset, and the test may need to be repeated on a later sample. Immunoglobulin G (IgG) antibodies may persist for years following asymptomatic or symptomatic infection, and the presence of IgG antibodies alone only provides evidence of previous infection.[36][37]
Confirmatory testing with a plaque reduction neutralisation test (PRNT) or molecular testing may be required.
Result
positive
plaque reduction neutralisation test
Test
PRNT is recommended for confirmatory testing and to determine the specific flavivirus. Confirmatory testing is required in certain circumstances (e.g., possible exposure to cross-reactive flaviviruses, atypical or unusually severe clinical presentation or death, presentation outside typical arboviral season, unusual route of transmission suspected such as an organ transplant or blood transfusion).[36][37]
PRNT on acute and convalescent serum specimens is recommended. A fourfold or greater change in WNV-specific neutralising antibody titre between acute and convalescent serum samples collected 7-10 days apart (or some sources recommend 2-3 weeks apart) confirms an acute infection. If neutralising antibodies are not detected, consider an alternative diagnosis.[36][37]
Result
positive
cerebrospinal fluid (CSF) analysis
full blood count
Test
Order when neuroinvasive disease is suspected.
Result
may show leukocytosis, anaemia, lymphopenia, thrombocytopenia
serum electrolytes
Test
Order when neuroinvasive disease is suspected.
Result
may show hyponatraemia
liver function tests
Test
Order when moderate to severe abdominal pain (especially right upper quadrant pain) or jaundice is present.[4] If elevated, this suggests hepatitis, a rare complication.
Result
elevated
serum amylase/lipase
Test
Order when moderate to severe abdominal pain (especially epigastric) or jaundice is present.[49] If elevated, this suggests pancreatitis, a rare complication.
Result
elevated
Investigations to consider
MRI brain
Test
Perform if suspicious of other causes of neurological symptoms.[40] Not diagnostic, but can help to exclude other causes of meningitis, encephalitis, and flaccid paralysis. Can also identify stroke, abscess, or other mass.
MRI is preferred over CT; however, CT is usually more readily available.
Result
may be normal or may show prominent signal abnormalities in the deep grey matter and/or cerebellum
CT head
Test
Perform if suspicious of other causes of neurological symptoms.[40] Not diagnostic, but can help to exclude other causes of meningitis, encephalitis, and flaccid paralysis. Can also identify stroke, abscess, or other mass.
Result
usually normal
reverse transcriptase-polymerase chain reaction (RT-PCR)
Test
Molecular testing (e.g., RT-PCR) may be recommended to confirm the diagnosis in certain circumstances.[36][37]
Molecular testing is recommended in conjunction with serological testing for immunocompromised patients (including those on B-cell depleting immunotherapies such as rituximab) to confirm the diagnosis, as immunocompromised patients can have prolonged viraemia and delayed antibody responses.[36][37]
Molecular testing can be performed on serum, plasma, CSF, or tissues. A positive result confirms the diagnosis. However, a negative result does not necessarily rule out infection. Viral RNA is usually negative by the time patients present with symptoms, and so is only useful early in the course of illness.[36][37] One study found that RT-PCR can identify WNV RNA in 86% of whole-blood samples during acute infection.[38]
Sensitivity is <60% in immunocompetent patients, and the likelihood of detecting an infection with molecular testing in an immunocompetent patient is fairly low.[36][37]
Result
virus isolation or viral RNA detected
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